Publications by Giovanni Ciriello

CellCharter reveals spatial cell niches associated with tissue remodeling and cell plasticity

Albert Santamaria Martinez, Giovanni Ciriello, Daniele Tavernari

Tissues are organized in cellular niches, the composition and interactions of which can be investigated using spatial omics technologies. However, systematic analyses of tissue composition are challenged by the scale and diversity of the data. Here we pres ...

Nature Portfolio2023

Whole-genome doubling drives oncogenic loss of chromatin segregation

Elisa Oricchio, Natalya Katanayeva, Ruxandra-Andreea Lambuta, Juan Diaz Miyar, Giovanni Ciriello, Daniele Tavernari

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies(1-8). However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotyp ...

NATURE PORTFOLIO2023

Cis-regulatory effect of HPV integration is constrained by host chromatin architecture in cervical cancers

Giovanni Ciriello, Daniele Tavernari

Human papillomavirus (HPV) infections are the primary drivers of cervical cancers, and often HPV DNA gets integrated into the host genome. Although the oncogenic impact of HPV encoded genes is relatively well known, the cis-regulatory effect of integrated ...

Wiley2023

Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL

Freddy Radtke, Ute Koch, Christelle Dubey, Nadine Fournier, Marianne Nkosi, Tara Kimberly Sugrue, Mateusz Waldemar Antoszewski, Giovanni Ciriello

NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 signaling launches a leukemia-prone chromatin landscape du ...

AMER SOC HEMATOLOGY2022

Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Elisa Oricchio, Natalya Katanayeva, Stephanie Jocelyne Sungalee, Ruxandra-Andreea Lambuta, Giovanni Ciriello, Daniele Tavernari

In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer-promoter interactions is a ...

2021

Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING

Christian Iseli, Julien Dorier, Mauro Delorenzi, Alizée Jéléna Grimm, Marco Mina, George Coukos, Alexandre Harari, Giovanni Ciriello

In this study, we investigate mechanisms leading to inflammation and immunoreactivity in ovarian tumors with homologous recombination deficiency (HRD). BRCA1 loss is found to lead to transcriptional reprogramming in tumor cells and cell-intrinsic inflammat ...

2021

Cancer Cells Retrace a Stepwise Differentiation Program during Malignant Progression

Douglas Hanahan, Krisztian Homicsko, Stephan Wullschleger, Mohammad Sadegh Saghafinia, Iacovos Michael, Giovanni Ciriello

Pancreatic neuroendocrine tumors (PanNET) comprise two molecular subtypes, relatively benign islet tumors (IT) and invasive, metastasis-like primary (MLP) tumors. Until now, the origin of aggressive MLP tumors has been obscure. Herein, using multi-omics ap ...

AMER ASSOC CANCER RESEARCH2021

Systematic inference and comparison of multi-scale chromatin sub-compartments connects spatial organization to cell phenotypes

Marco Mina, Elisa Oricchio, Stephanie Jocelyne Sungalee, Giovanni Ciriello, Daniele Tavernari

Chromatin compartmentalization reflects biological activity. However, inference of chromatin sub-compartments and compartment domains from chromosome conformation capture (Hi-C) experiments is limited by data resolution. As a result, these have been charac ...

Nature Research2021

Cathepsin S Regulates Antigen Processing and T Cell Activity in Non-Hodgkin Lymphoma

Julien Racle, Jessica Sordet, Marco Mina, George Coukos, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Natalya Katanayeva, Elena Battistello, Stephanie Jocelyne Sungalee, Elie Charles Eugène Dheilly, Sarah Wehrle, Giovanni Ciriello

Genomic alterations in cancer cells can influence the immune system to favor tumor growth. In non-Hodgkin lymphoma, physiological interactions between B cells and the germinal center microenvironment are coopted to sustain cancer cell proliferation. We fou ...

2020

Synaptic proximity enables NMDAR signalling to promote brain metastasis

Graham Knott, Douglas Hanahan, Mohammad Sadegh Saghafinia, Iacovos Michael, Qiqun Zeng, Brian Donal McCabe, Wei Jiao, Giovanni Ciriello, Peng Zhang, Inti Zlobec

Metastasis-the disseminated growth of tumours in distant organs-underlies cancer mortality. Breast-to-brain metastasis (B2BM) is a common and disruptive form of cancer and is prevalent in the aggressive basal-like subtype, but is also found at varying freq ...

2019

EZH2 oncogenic mutations drive epigenetic, transcriptional, and structural changes within chromatin domains

Suliana Manley, Marco Mina, Kyle Michael Douglass, Elisa Oricchio, Natalya Katanayeva, Maria Christine Donaldson, Elena Battistello, Timo Henry René Rey, Stephanie Jocelyne Sungalee, Giovanni Ciriello, Daniele Tavernari

Chromatin is organized into topologically associating domains (TADs) enriched in distinct histone marks. In cancer, gain-of-function mutations in the gene encoding the enhancer of zeste homolog 2 protein (EZH2) lead to a genome-wide increase in histone-3 L ...

2019

Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors

Douglas Hanahan, Marco Mina, Mohammad Sadegh Saghafinia, Giovanni Ciriello

The discovery of cancer-associated alterations has primarily focused on genetic variants. Nonetheless, altered epigenomes contribute to deregulate transcription and promote oncogenic pathways. Here, we designed an algorithmic approach (RESET) to identify a ...

2018

Comparison of computational methods for the identification of topologically associating domains

Marie-Pierre Zufferey, Elisa Oricchio, Giovanni Ciriello, Daniele Tavernari

BackgroundChromatin folding gives rise to structural elements among which are clusters of densely interacting DNA regions termed topologically associating domains (TADs). TADs have been characterized across multiple species, tissue types, and differentiati ...

2018

Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma

Olivier Michielin, Elisa Oricchio, Natalya Katanayeva, Maria Christine Donaldson, Elena Battistello, Elie Charles Eugène Dheilly, Giovanni Ciriello, Daniele Tavernari

2018

Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma

Elisa Oricchio, Natalya Katanayeva, Maria Christine Donaldson, Elena Battistello, Stephanie Jocelyne Sungalee, Giovanni Ciriello

Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focu ...

American Association for the Advancement of Science2017

Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies

Marco Mina, Franck Claude Raynaud, Mohammad Sadegh Saghafinia, Titouan Laessle, Elisa Oricchio, Elena Battistello, Stephanie Jocelyne Sungalee, Giovanni Ciriello, Daniele Tavernari

Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the ...

Cell Press2017

Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells

Elisa Oricchio, Giovanni Ciriello

The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-defi ...

Cell Press2016

Frequent disruption of the RB pathway in indolent follicular lymphoma suggests a new combination therapy

Elisa Oricchio, Giovanni Ciriello

Loss of cell cycle controls is a hallmark of cancer and has a well-established role in aggressive B cell malignancies. However, the role of such lesions in indolent follicular lymphoma (FL) is unclear and individual lesions have been observed with low freq ...

2014